rs7122693

Variant names:

• chr11-115433644-A-G
• rs7122693
• NM_001301043.2:c.124+70627T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301043.2(CADM1):​c.124+70627T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,108 control chromosomes in the GnomAD database, including 8,827 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8827 hom., cov: 32)
• Consequence: CADM1 NM_001301043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 8 publications found

Genes affected

CADM1 (HGNC:5951): (cell adhesion molecule 1) Enables signaling receptor binding activity. Involved in several processes, including cell recognition; positive regulation of cytokine production; and susceptibility to natural killer cell mediated cytotoxicity. Located in plasma membrane. Implicated in breast carcinoma and prostate cancer. Biomarker of cervix uteri carcinoma in situ. [provided by Alliance of Genome Resources, Apr 2022]

CADM1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM1	NM_001301043.2	c.124+70627T>C		intron_variant	Intron 1 of 11	ENST00000331581.11	NP_001287972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM1	ENST00000331581.11	c.124+70627T>C		intron_variant	Intron 1 of 11	1	NM_001301043.2	ENSP00000329797.6

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48637 AN: 151992 Hom.: 8825 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.320 AC: 48653 AN: 152108 Hom.: 8827 Cov.: 32 AF XY: 0.314 AC XY: 23350 AN XY: 74336

African (AFR) AF: 0.173 AC: 7189 AN: 41490

American (AMR) AF: 0.238 AC: 3640 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3466

East Asian (EAS) AF: 0.208 AC: 1077 AN: 5176

South Asian (SAS) AF: 0.204 AC: 986 AN: 4824

European-Finnish (FIN) AF: 0.443 AC: 4687 AN: 10582

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29086 AN: 67982

Other (OTH) AF: 0.311 AC: 657 AN: 2110

Alfa AF: 0.377 Hom.: 36726

Bravo AF: 0.298

Asia WGS AF: 0.217 AC: 757 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		-0.048
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7122693; hg19: chr11-115304363;